Serotonin (5-HT) administered at 1, 3, and 10 microM into the striatum of halothane-anesthetized rats by in vivo microdialysis increased extracellular dopamine (DA) in a concentration-dependent manner (approximately 65, 190, and 440%, respectively). These effects were reduced by 50% in the presence of 1 microM tetrodotoxin (TTX) or in the absence of Ca2+ ions. The DA uptake blocker nomifensine (0.1 microM) significantly lowered (by 50%) the enhancement of DA outflow induced by 3 microM 5-HT. Nomifensine (1 microM) coperfused with 1 microM TTX abolished the 1 and 3 microM 5-HT-induced DA outflow, whereas the effect of 10 microM 5-HT was significantly reduced by 1 (-55%) and 10 micro M (-70%) nomifensine. These data demonstrate that, in vivo, striatal DA uptake sites are partially involved in the DA-releasing action of 5-HT.